Vacuolar protein sorting-associated protein VTA1 homolog (VTA1)
The protein contains 307 amino acids for an estimated molecular weight of 33879 Da.
Involved in the endosomal multivesicular bodies (MVB) pathway. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. Thought to be a cofactor of VPS4A/B, which catalyzes disassembles membrane-associated ESCRT-III assemblies. Involved in the sorting and down-regulation of EGFR (By similarity). Involved in HIV-1 budding. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs2232307 |
Biological Process
Endosomal transport
ESCRT III complex disassembly
Late endosome to vacuole transport via multivesicular body sorting pathway
Macroautophagy
Membrane organization
Multivesicular body assembly
Multivesicular body sorting pathway
Protein transport
Viral budding
Viral life cycle
Viral process
The reference OMIM entry for this protein is 610902
Chromosome 6 open reading frame 55; c6orf55
Skd1-binding protein 1; sbp1
Lyst-interacting protein 5; lip5
Vta1, yeast, homolog of; vta1
Dopamine-responsive gene 1; drg1
DESCRIPTION
C6ORF55 encodes a protein involved in trafficking of the multivesicular body, an endosomal compartment involved in sorting membrane proteins for degradation in lysosomes (Ward et al., 2005).CLONING
Using subtractive hybridization to identify genes upregulated by dopamine in rat cerebral astrocytes, followed by screening a human fetal brain cDNA library, Shi et al. (2001) cloned C6ORF55. The transcript contains a novel (CAG)n repeat that encodes polyglutamines. Using yeast 2-hybrid analysis to screen human cDNA libraries for genes encoding LYST (606897)-interacting proteins, Tchernev et al. (2002) cloned C6ORF55, which they called LIP5. Using Skd1 (VPS4B; 609983) as bait in a yeast 2-hybrid screen of a mouse brain cDNA library, Fujita et al. (2004) cloned C6orf55, which they called Sbp1. By database analysis, they identified multiple human cDNAs corresponding to SBP1, including 2 that encode 307- and 282-amino acid proteins, designated DRG1 and LIP5, respectively, that are identical in their first 157 amino acids but differ in their C termini. Fujita et al. (2004) suggested that these cDNAs encode distinct proteins due to small sequence alterations rather than alternative splicing. The deduced 309-amino acid mouse protein contains N- and C-terminal coiled-coil domains. The N-terminal region of SBP1 is rich in basic amino acids, whereas the C-terminal region is acidic. Northern blot analysis detected Sbp1 expression in most mouse tissues examined, with highest levels in heart, brain, liver, and kidney. Immunofluorescence analysis of HeLa cells showed that endogenous human SBP1 localized to the cytosol. By sequence analysis, Ward et al. (2005) determined that the LIP5 cDNA encoding the 282-amino acid protein contains a frameshift, and that the full-length LIP5 protein contains 307 amino acids. Cell fractionation of COS-7 cells followed by Western blot analysis showed that epitope-tagged LIP5 was primarily cytosolic.GENE FUNCTION
By yeast 2-hybrid analysis and pull-down assays, Fujita et al. (2004) showed that the C-terminal region of mouse Sbp1 bound Skd1. Expression of an ATPase-negative mouse Skd1 mutant in HeLa cells redirected endogenous SBP1 and SKD1 from the cytosol to an aberrant endosomal structure derived from early and late endosomes and lysosomes. In control HeLa cells, SKD1 existed as a monomer, and SBP1 formed an oligomer protein complex. The ATPase-negative Skd1 mutant formed large heterooligomers with endogenous SBP1 and SKD1 when expressed in HeLa cells, suggesting that the ATPase activity of SKD1 is required for disassembly of the SBP1/SKD1 complex. Using affinity purification experiments, Ward et al. (2005) showed that LIP5 specifically interacted with CHMP5 (610900). Depletion of LIP5 by small-interfering RNA did not alter the distribution of early or late endocytic markers in HeLa and 293T cells, but it altered EGFR (131550) trafficking and reduced EGFR degradation in lysosomes. Depletion of LIP5 in 293T cells infected with human immunodeficiency virus (HIV)-1 reduced release of infectious particles.MAPPING
By genomic sequence analysis, Fujita et al. (2004) mapped the C6ORF55 gene to chromosome 6. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610902 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed